A polyoxyalkylene polymer obtained by ring-opening polymerization of a cyclic ether compound, for example, an alkylene oxide to a starting substance having an active hydrogen is non-antigenic, excellent in biocompatibility, and used in use, for example, a wound covering material, an antiadhesive material, a drug sustained-release material or a scaffold material in regenerative medicine, in the field of medical material. Among them, a polyoxypropylene/polyoxyethylene block copolymer is able to arbitrarily adjust swellability, flexibility, mechanical strength or cell•tissue adhesiveness by changing composition of a hydrophobic polyoxypropylene and a hydrophilic polyoxyethylene, and is widely utilized as the medical material because of its high versatility.
Production of the polyoxyalkylene polymer is ordinarily performed by ring-opening polymerization of an alkylene oxide to a starting substance having an active hydrogen in the presence of a base catalyst. However, when the ring-opening polymerization of propylene oxide is performed using a base catalyst, isomerization of propylene oxide occurs to generate allyl alcohol in parallel with the polymerization reaction of propylene oxide. The allyl alcohol generated acts as a new polymerization starting point to perform ring-opening polymerization of a propylene oxide and as a result, the polyoxypropylene polymer contains polyoxypropylene monoallyl ether.
A polyoxypropylene/polyoxyethylene block copolymer is obtained by ring-opening polymerization of ethylene oxide to a polyoxypropylene polymer. In this case, when the polyoxypropylene polymer contains polyoxypropylene monoallyl ether derived from the isomerization of propylene oxide, ethylene oxide is also polymerized from a hydroxy group of the polyoxypropylene monoallyl ether and as a result, monoallyl ether of polyoxypropylene/polyoxyethylene block copolymer is by-produced.
The presence of an unsaturated ether, for example, the ally ether, in the polyoxypropylene polymer and the polyoxypropylene/polyoxyethylene block copolymer leads to substantial decrease in hydroxy group number and in the case where the hydroxy group is subjected to chemical conversion to other functional group to use as the medical material, the function thereof is impaired. Also, the unsaturated ether is likely to exert an adverse influence on the physical property of the medical material by an unexpected surface active effect, a side reaction or the like.
It has hitherto been known that allyl ether by-produced in the ring-opening polymerization of propylene oxide is isomerized to propenyl ether by a catalytic action of the base and the propenyl ether is further hydrolyzed into propionaldehyde and a hydroxy group by an acid treatment (Non-Patent Document 1). There are many prior examples relating to decrease of an unsaturated ether (allyl ether and propenyl ether are collectively referred to as an unsaturated ether, this is also the same hereinafter) based on this methodology. However, the decrease of an unsaturated ether is not so easy in practice, and in almost all the prior examples, the unsaturated ether remains in a large amount.
For example, in Patent Document 1, a method of isomerization of allyl ether to propenyl ether using potassium hydroxide or sodium methoxide and subsequent hydrolysis of the propenyl ether is described. In the method described herein, although the treatment is conducted at 120° C. using a hydroxide of alkali metal or a primary or secondary alkoxide of alkali metal as the base catalyst, an isomerization efficiency of allyl ether to propenyl ether is low and after the subsequent hydrolysis of the propenyl ether, the unsaturated ether remains in a large amount.
As an example capable of sufficiently decreasing the unsaturated ether content, Non-Patent Document 2 is exemplified. The unsaturated ether is almost removed by treating at 160° C. for 3 hours after ring-opening polymerization of propylene oxide in the presence of about 10% by mole of potassium hydroxide based on a hydroxy group of glycerol, and then conducting a mineral acid treatment. However, according to the method described here, since it is necessary to treat at high temperature of 160° C. for a long period of time in order to isomerize allyl ether, it has a fault in that the polyoxypropylene polymer is apt to be colored. Since the colored article is recused in the field of medical material, development of a method which sufficiently decreases the unsaturated ether content and suppresses the coloring is of great significance.
On the other hand, since allyl ether is isomerized to propenyl ether also by only an acid catalyst, in Patent Document 2, the unsaturated ether content is decreased by adding a mineral acid to the polyoxypropylene polymer after the ring-opening polymerization of propylene oxide to adjust pH from 2 to 4 and then treating at 80 to 150° C. However, in the method described here the isomerization efficiency of allyl ether is low, and although there is a possibility to more decrease the unsaturated ether by treating at lower pH or high temperature, the quality degradation, for example, generation of a pungent odor occurs so that it is not adequate as the production method of the medical material.
Also, in Patent Document 3, the unsaturated ether contained in the polyoxypropylene/polyoxyethylene block copolymer is removed by gel permeation chromatography, and the polyoxypropylene/polyoxyethylene block copolymer which does not contain the unsaturated ether is used as the medical material. However, the method described here has the difficulty of applying it to an industrial scale because of problems in technical aspect and cost.
As described above, with respect to the production method of polyoxypropylene polymer and polyoxypropylene/polyoxyethylene block copolymer in which the unsaturated ether content is low and the coloring is suppressed, an example which can be easily performed on the industrial scale has not been known.